DESCRIPTION: (Principal Investigator's) The major goal of this proposal is to discover and develop fundamental new chemistry in the emerging field of supramolecular dendrimer chemistry. The proposed effort has a special focus on organic modules which noncovalently interact to form discrete assemblies and o strategies for increasing the binding capacity of dendritic hosts. Although no a goal in the next five years, this work may ultimately facilitate new applications of dendrimers to problems of biomedical significance. In particular, dendrimers have considerable promise as drug delivery devices because their peripheral groups may solubilize them in water and allow specifi cells, tissues, or proteins to be targeted while their interiors can carry small molecules (e.g., drugs). The major limitation of dendrimers as drug delivery vehicles is their rather modest capacity, with only a few copies of average-sized organic molecules being carried by large (5th or 6th generation) dendrimers. We will accomplish these goals by (1) completing ongoing studies on self-assembling dendrimers in organic solvents and extending these efforts toward higher order aggregates, (2) the synthesis and study of hydrophobically driven assembly processes, and (3) by chemical cross-linking of dendrimer surfaces and chemical excision of their cores. The self-assembling organic modules that we will develop form donut-shaped or helical, tubular superstructures with dendritic peripheral substituents and internal voids. These self-assembled structures will be covalently captured by chemical cross-linking of the dendrimers. Alternatively, a novel strategy will be purse for the synthesis of "hollow dendrimer." The strategy involves the chemical cross-linking of a dendrimer surface, followed by the chemical cleavage of labile internal bonds to chemically excise the core.